Recognizing Hypercortisolism Prevalence in Uncontrolled Hypertension, T2D
An expert discusses how delayed diagnosis of hypercortisolism leads to serious cardiometabolic, skeletal, and psychiatric consequences, while evolving understanding of its often subtle, variable presentation continues to challenge timely detection.
By
Bob Busch, MD
| Published on October 29, 2025
2 min read
A delayed or missed diagnosis of hypercortisolism has profound health consequences, as prolonged exposure to excess cortisol leads to progressive multisystem damage. Pivonello (2016) notes that undiagnosed or untreated patients face significantly increased risks of cardiometabolic abnormalities, including hypertension, insulin resistance, dyslipidemia, and central obesity, all of which elevate cardiovascular disease risk. In addition, cortisol’s catabolic effects contribute to osteoporosis, muscle wasting, and skin fragility, while neuropsychiatric complications such as depression, anxiety, and cognitive decline further impair quality of life. The combination of these comorbidities results in an increased mortality rate compared to the general population, emphasizing the critical importance of timely recognition and treatment.
Over time, the clinical understanding of hypercortisolism has shifted from focusing on its classic, overt features—such as “moon face,” “buffalo hump,” and purple striae—to recognizing that many patients present with subtle or nonspecific symptoms overlapping with common chronic diseases. According to the Endocrine Society Guidelines (2008), many cases now identified represent mild or subclinical hypercortisolism rather than the dramatic presentations historically associated with Cushing syndrome. This evolution reflects improved awareness and diagnostic sensitivity but also underscores the diagnostic challenge, as symptoms like fatigue, weight gain, and mood changes are easily attributed to other conditions.
The broad spectrum of hypercortisolism’s clinical manifestations complicates clinicians’ ability to diagnose the disorder accurately and promptly. Because cortisol excess affects nearly every organ system, no single sign is pathognomonic, and symptom combinations vary greatly among patients. This heterogeneity often leads to diagnostic uncertainty, delayed referrals, or misattribution to more prevalent disorders such as diabetes, depression, or obesity. Consequently, clinicians must maintain a high index of suspicion—particularly in patients with multiple, progressive, and treatment-resistant comorbidities—to ensure earlier detection and prevent long-term complications.
